Anterior mediastinal neuroblastoma in an adult: an additional case of a rare tumor in an unusual location with review of the literature.

Neuroblastoma is rare in the adult population, especially in thoracic or mediastinal locations, with only 25 previously reported cases. We report an additional example of primary thymic neuroblastoma in a previously asymptomatic 71-year-old man with an anterior mediastinal mass who underwent robotic excision with pericardium and adjacent lung. The tumor was a 5.2 cm partially encapsulated, white-tan and rubbery mass with grossly identifiable areas of necrosis (25%) and hemorrhage. Histologically, the specimen showed a rim of adipose tissue and residual thymic tissue with areas of cystic thymic epithelium and prominent lymphoid tissue containing Hassall's corpuscles. The tumor was composed of uniform, round cells with scant cytoplasm and small nuclei with inconspicuous nucleoli set within a background of conspicuous neuropil. Mitotic figures were easily found. By immunohistochemistry, the tumor cells expressed synaptophysin, chromogranin, NKX2.2 (diffuse, nuclear), GFAP (patchy), SMI31 (neurofilament) (focal, cytoplasmic), and TdT (diffuse, nuclear), while lacking expression of CD99, TTF-1, CK 20, MCPyV, PHOX2B, Olig2, OCT3/4, CD45, CD3 and PAX5. S100 protein was negative in the neuroblastic cells, with scattered positive cells in a vague sustentacular-like pattern. Fluorescence in situ hybridization for isochromosome 12p and EWSR1 gene rearrangement were negative. As thymic neuroblastoma is extremely rare in adults, a neuroblastic tumor of germ cell origin (either primary or metastatic) or spread from a sinonasal tract tumor should be excluded because of differing treatments and prognoses. The properties of these rare neoplasms appear similar to olfactory neuroblastoma rather than pediatric-type neuroblastoma.

Primary mediastinal seminoma with florid follicular lymphoid hyperplasia: a case report and review of the literature.

BACKGROUND: First described in 1955 Primary mediastinal seminomas are rare. Only 1-4% of mediastinal tumours are germ cell tumors; majority of which are teratomas. They typically present in men aged between 20 and 40 years. Very few cases are reported in the literature. Florid follicular lymphoid hyperplasia can obscure the malignant cells and is a rarer finding still. We present a rare case of a 48 year old man with a primary mediastinal seminoma with florid follicular lymphoid hyperplasia; found following excision of a clinically presumed thymoma. CASE PRESENTATION: A 48 year old man was referred for excision of a thymic mass. The presumed diagnosis was a thymoma; following preoperative investigations. The mass was incidentally found on a radiological imaging. However, the patient did report mid-sternal discomfort on lying flat and breathlessness. The patient underwent a thymectomy via a partial median sternotomy with good recovery. Histological assessment was that the mass was in fact a primary mediastinal seminoma with florid follicular lymphoid hyperplasia. A primary testicular malignancy was excluded and the patient required no further oncological treatment. CONCLUSIONS: Only 11 cases have previously been reported of primary mediastinal seminoma with florid follicular lymphoid hyperplasia. Although rare, a primary mediastinal seminoma should be considered as a differential diagnosis for presentations with a thymic mass. Tumour markers can be helpful, however are only positive in third of cases. Ultrasound imaging of the gonads is essential to exclude a primary gonadal lesion. Pure seminomas are radiotherapy and chemotherapy sensitive however the mainstay treatment of primary mediastinal seminomas remains surgical excision. Radiotherapy is reserved postoperatively for incomplete surgical margins.

A multilocular thymic cyst associated with mediastinal seminoma: evidence for its medullary epithelial origin highlighted by POU2F3-positive thymic tuft cells and concomitant myoid cell proliferation.

Multilocular thymic cyst (MTC) and germ cell tumors are common diseases that impact the mediastinum. Correctly diagnosing these diseases can be difficult because several other conditions can mimic them. We report a male patient with MTC associated with mediastinal seminoma. A needle biopsy of the mediastinal tumor revealed numerous epithelioid cell granulomas that mimicked sarcoidosis or mycobacterial infection. However, large atypical cells positive for Oct3/4 and KIT were noted between the granulomas; thus, we diagnosed the patient with mediastinal seminoma. The resected tumor, after chemotherapy, consisted of multiple cystic lesions, and a residual germ cell tumor was first considered. However, thymic medulla-specific elements, namely, POU2F3-positive thymic tuft cells and rhabdomyomatous myoid cells accompanying the epithelium, led to the correct diagnosis of MTC. Our case underscores the importance of recognizing the histological features associated with mediastinal seminoma and provides novel findings for MTC pathogenesis, namely, the presence of thymic tuft cells.

Vasculogenic Mesenchymal Tumor: A Clinicopathologic and Molecular Study of 55 Cases of a Distinctive Neoplasm Originating From Mediastinal Yolk Sac Tumor and an Occasional Precursor to Angiosarcoma.

We report 55 postchemotherapy resections of primary nonseminomatous mediastinal germ cell tumors with prominent vasculogenic features showing the formation of rudimentary to well-developed neoplastic vessels within primitive mesenchyme. These cases represented 25% of a cohort of 221 such specimens. The patients were 19 to 49 years old (mean, 28 y) and 98% had serological evidence of yolk sac tumor. The vasculogenic lesions, felt to represent a neoplastic reiteration of embryonic vasculogenesis in the splanchnic mesoderm of the yolk sac, were further subdivided into teratoma with vasculogenic stroma (n=9), vasculogenic mesenchymal tumor (VMT) (n=42, further classified into low grade [n=24] and high grade [n=18]), and angiosarcoma (n=4). The distinction of teratoma with vasculogenic stroma from VMT was based solely on the greater extent of VMT (exceeding 1 low power [×4 objective] microscopic field), with both categories showing a spectrum of vessels lined by atypical endothelium in a nonendothelial neoplastic stroma that often also generated vascular walls comprised of atypical smooth muscle. The angiosarcomas showed stratification of highly atypical endothelial cells or anastomosing vessels lined by nonstratified but cytologically similar endothelium. Immunohistochemical studies supported the generation of neoplastic vessels from the tumor stroma, most commonly by the development of stromal clefts showing reactivity for podoplanin, CD34, and occasionally ERG, followed by the gradual development from the clefts of thin-walled vessels that later became encircled by stromal cells showing smooth muscle differentiation by immunohistochemistry. Occasionally, round collections of stromal erythrocytes became surrounded by stromal cells to generate blood vessels. Fluorescence in situ hybridization showed chromosome 12p copy number increase in both the endothelial component and stromal component in 8/9 VMT cases and in 1/1 angiosarcoma. On follow-up, no patient with teratoma with vasculogenic stroma had evidence of a subsequent vascular tumor or sarcoma, whereas 8 of the 35 (23%) patients with VMTs (2 low grade and 6 high grade) and meaningful follow-up developed sarcoma (1 angiosarcoma, 2 rhabdomyosarcomas, and 5 not further characterized). The difference between low-grade and high-grade tumors was of borderline significance (P=0.058). Two of the 4 patients with angiosarcoma died of metastatic angiosarcoma, with the other 2 disease-free at 6.8 and 7 years. Compared with the 165 patients with follow-up and no vasculogenic lesions, there was a highly significant (P=4.3×10-5) association of any vasculogenic lesion with sarcomatoid tumors during the clinical course of VMT patients. In addition, 5/46 patients with follow-up and vasculogenic lesions (11%) died of either leukemia or myelodysplastic syndrome compared with 2 of 166 (1%) lacking them (P=0.0012). Three of the 5 patients had identifiable immature hematopoietic cells within their vasculogenic lesions, but 4 other VMT patients with these did not develop leukemia or myelodysplasia. We conclude: (1) vasculogenic lesions are frequent in postchemotherapy resections of primary mediastinal germ cell tumors with yolk sac tumor components; (2) they mostly consist of neoplastic vessels in a stroma that also generates neoplastic vascular walls of smooth muscle; (3) VMTs are associated with an increased incidence of sarcomas, even though most vasculogenic lesions in this context do not meet criteria for angiosarcoma; (4) the presence of vasculogenic lesions in postchemotherapy resections of primary mediastinal germ cell tumors place patients at increased risk for leukemia or myelodysplasia.

Water-Clear Cell Adenoma of the Mediastinal Parathyroid Gland.

Water-clear cell adenoma of the parathyroid gland is a rare neoplasm that consists of cells with abundant clear-pink cytoplasm. There have only been 19 cases reported in the English literature. Here we report a case of water-clear cell adenoma of the mediastinal parathyroid gland. A 70-year-old male patient presented to the hospital with back pain and a mediastinal mass 6 cm in size was detected. After excision and microscopic evaluation, uniform, large clear cells with fine cytoplasmic vacuolization, without nuclear atypia, and arranged in solid and acinar patterns were revealed. The cells formed nests that were separated by fine fibrovascular septae and stained positively with anti-parathyroid hormone. To the best of our knowledge, this has not been previously reported in this location. In the differential diagnosis of clear cell lesions of the mediastinum, water-clear cell parathyroid adenoma should be considered.

Both serum and tissue Galectin-1 levels are associated with adverse clinical features in neuroblastoma.

BACKGROUND: Neuroblastoma is one of the most common pediatric solid tumors. Although the 5-year overall survival rate has increased over the past few decades, high-risk patients still have a poor prognosis due to a lack of biomonitoring therapy. This study was performed to investigate the role of Galectin-1 in neuroblastoma biomonitoring therapy. PROCEDURE: A tissue microarray containing 37 neuroblastoma tissue samples was used to evaluate the correlation between Galectin-1 expression and clinical features. Blood samples were examined to better understand whether serum Galectin-1 (sGalectin-1) could be used for biomonitoring therapy. Kaplan-Meier analysis and ROC analysis was conducted to distinguish the outcome associated with high or low expression of Galectin-1 in patients with neuroblastoma. RESULTS: Increased Galectin-1 expression was found in neuroblastoma and it was further demonstrated that elevated tissue Galectin-1 expression was related to INSS stage, histology, bone marrow metastasis, and poor survival. sGalectin-1 levels were higher in newly diagnosed patients with neuroblastoma than healthy subjects. Patients with elevated sGalectin-1 through treatment cycles correlated with the poor chemo-responses and tended to have worse outcomes, such as metastasis or stable tumor size, whereas gradually decreasing sGalectin-1 levels correlated with no observed progression in clinical symptoms. CONCLUSIONS: Tissue and serum Galectin-1 levels were associated with adverse clinical features in patients with neuroblastoma, and sGalectin-1 could be a potential biomarker for monitoring therapy.

J chain and myocyte enhancer factor 2B are useful in differentiating classical Hodgkin lymphoma from nodular lymphocyte predominant Hodgkin lymphoma and primary mediastinal large B-cell lymphoma.

Although most classical Hodgkin lymphomas (CHLs) are easily distinguished from nodular lymphocyte predominant Hodgkin lymphoma (NLPHL) and primary mediastinal large B-cell lymphoma (PMBL), cases with significant CD20 expression cause diagnostic confusion. Although the absence of OCT-2 and BOB.1 are useful in these circumstances, a variable proportion of CHLs are positive for these antigens. We investigated the utility of J chain and myocyte enhancer factor 2B (MEF2B) in the diagnosis of CHL; NLPHL; PMBL; T-cell/histiocyte-rich large B-cell lymphoma (TCRLBL); and B-cell lymphoma, unclassifiable, with features intermediate between diffuse large B-cell lymphoma and CHL, compared with OCT-2 and BOB.1. J chain and MEF2B highlighted lymphocyte predominant (LP) cells in 20/20 (100%) NLPHLs and were negative in 43/43 (100%) CHLs. Fourteen of 15 (93%) PMBLs and 4/4 (100%) TCRLBLs were MEF2B positive, whereas 67% of PMBLs and 50% of TCRLBLs were J chain positive. Three of 3 B-cell lymphomas, unclassifiable, with features intermediate between diffuse large B-cell lymphoma and CHL, were negative for J chain and MEF2B. J chain and MEF2B were 100% sensitive and specific for NLPHL versus CHL. MEF2B was 100% sensitive and 98% specific for PMBL versus CHL. Whereas loss of OCT-2 and/or BOB.1 expression had a sensitivity of only 86% and specificity of 100% for CHL versus NLPHL, PMBL, and TCRLBL, lack of both J chain and MEF2B expression was 100% sensitive and 97% specific. J chain and MEF2B are highly sensitive and specific markers of NLPHL versus CHL; are particularly useful in highlighting LP cells; and, with rare exception, are of greater utility than OCT-2 and BOB.1 in differentiating CHL from NLPHL and other large B-cell lymphomas.

Soft tissue metastasis of mediastinal non-functioning paraganglioma with unusual TTF-1 expression: a potential diagnostic pitfall.

Metastatic extra-adrenal paragangliomas are very rare and can represent diagnostic challenges. We report a case of 69-year-old man with a tumor of the right shoulder. Histologic and immunohistochemical examinations confirmed the diagnosis of paraganglioma. Surprisingly, tumor cells were diffusely thyroid transcription factor 1 (TTF-1) positive. Succinate dehydrogenase complex subunit B (SDHB) deficiency has not been detected. Inherited syndromes associated with paragangliomas were ruled out. The primary tumor was identified in the mediastinum. This is the first report of TTF-1 expression in paraganglioma. To avoid misdiagnosis, careful clinical and pathological examination of any tumor with organoid growths pattern is necessary.

Giant Leiomyoma Arising from the Mediastinal Pleura: A Case Report.

This report presents a rare case involving a patient with a giant leiomyoma originating from the mediastinal pleura. The patient underwent a medical examination, and chest radiography revealed a giant tumor. Computed tomography (CT) and magnetic resonance imaging (MRI) showed a well demarcated, heterogeneous mass which seemed to originate from the posterior mediastinum. Positron emission tomography (PET) showed the uptake of this tumor with a standardized uptake value of 4.9. We suspected that this tumor was a solitary fibrous tumor, and the patient underwent a surgical resection. Intraoperative exploration revealed a well-encapsulated tumor measuring 15 × 11 cm that appeared to originate from the mediastinal pleura. Immunohistochemical findings revealed a benign leiomyoma. We finally diagnosed the patient with a mediastinal leiomyoma. The present report describes CT, MRI, and PET findings of leiomyoma, and presents a review of relevant literature.

Glioblastoma arising within a mediastinal mature teratoma.

Herein we present the case of a 42-year-old man who presented with an anterior mediastinal mass, which was found to represent a mature teratoma. Within it, there was a secondary somatic malignant glial neoplasm with mitotic activity and necrosis, compatible with glioblastoma. He experienced early local recurrence and lymph node metastasis, but is alive and well 3 1/2 years after diagnosis. Neither the teratoma nor the glioblastoma components had abnormalities of chromosome 12, which may implicate that this teratoma was more closely related to those arising along the midline of infants and children (type I germ cell tumor) than to the typically malignant testicular examples, which often contain mixed germ cell elements (type II germ cell tumor).

ZBTB16: a novel sensitive and specific biomarker for yolk sac tumor.

Although the function of zinc finger and BTB domain containing 16 (ZBTB16) in spermatogenesis is well documented, expression of ZBTB16 in germ cell tumors has not yet been studied. The aim of this study was to investigate the immunohistochemical expression and diagnostic utility of ZBTB16 in germ cell tumors. A total of 67 adult germ cell tumors were studied (62 testicular germ cell tumors, 2 ovarian yolk sac tumors, 1 mediastinal yolk sac tumor, and 2 retroperitoneal metastatic yolk sac tumors). The 62 testicular primary germ cell tumors are as follows: 34 pure germ cell tumors (20 seminomas, 8 embryonal carcinomas, 2 teratomas, 1 choriocarcinoma, 1 carcinoid, and 2 spermatocytic tumors) and 28 mixed germ cell tumors (composed of 13 embryonal carcinomas, 15 yolk sac tumors, 15 teratomas, 7 seminomas, and 3 choriocarcinomas in various combinations). Thirty-five cases contained germ cell neoplasia in situ. Yolk sac tumor was consistently reactive for ZBTB16. Among the 15 testicular yolk sac tumors in mixed germ cell tumors, all displayed moderate to diffuse ZBTB16 staining. ZBTB16 reactivity was present regardless of the histologic patterns of yolk sac tumor and ZBTB16 was able to pick up small foci of yolk sac tumor intermixed/embedded in other germ cell tumor subtype elements. Diffuse ZBTB16 immunoreactivity was also observed in 2/2 metastatic yolk sac tumors, 1/1 mediastinal yolk sac tumor, 2/2 ovarian yolk sac tumors, 2/2 spermatocytic tumors, 1/1 carcinoid, and the spermatogonial cells. All the other non-yolk sac germ cell tumors were nonreactive, including seminoma (n=27), embryonal carcinoma (n=21), teratoma (n=17), choriocarcinoma (n=4), and germ cell neoplasia in situ (n=35). The sensitivity and specificity of ZBTB16 in detecting yolk sac tumor among the germ cell tumors was 100% (20/20) and 96% (66/69), respectively. In conclusion, ZBTB16 is a highly sensitive and specific marker for yolk sac tumor.

Mediastinal Granular Cell Tumor in a 16-Year-Old Boy: A Surgical and Pathologic Perspective.

Granular cell tumor is a benign tumor of likely neural or neuroectodermal origin that occurs most commonly in the subcutaneous tissues of the trunk, breast, and extremities of adults. Congenital gingival lesions comprise the majority of the pediatric granular cell tumors. Granular cell tumors are generally small and asymptomatic, and while 1 in 10 patients has multiple tumors, recurrence and malignancy are very rare. Mediastinal granular cell tumors have been reported, most occurring in young adult or middle-aged women. We present a case of a 16-year-old asymptomatic boy with a large mediastinal granular cell tumor incidentally identified after a motor vehicle accident, and we review the intraoperative, microscopic, and ultrastructural features of this tumor. Both the patient's age and anatomical location are unusual for this tumor, which presented technical and diagnostic challenges to the patient care team.

Discordant lymphoma consisting of mediastinal large B-cell lymphoma and nodular sclerosis Hodgkin lymphoma in the right supraclavicular lymph nodes: a case report.

BACKGROUND: Discordant lymphoma is defined by the simultaneous presence of two or more distinct types of lymphomas at different anatomic sites. With fewer than 20 studies reporting cases of discordant lymphoma to date, the incidence of this condition is believed to be very low. CASE PRESENTATION: Here, we report a case of discordant lymphoma in a 34-year-old female patient that involved mediastinal large B-cell lymphoma and nodular sclerosis Hodgkin lymphoma in the right supraclavicular lymph nodes. The patient presented with a mass in the mediastinum and enlargement of the right supraclavicular lymph nodes, but no obvious signs of lymphoma. Histological examination revealed that the encapsulated mediastinal mass contained medium- or large-size tumor cells with lightly stained cytoplasm and round vesicular nuclei as well as a high percentage of mitotic cells; strongly positive immunohistochemical staining for PAX5, CD20, and CD79a also was observed. Examination of biopsied right supraclavicular lymph node tissues revealed separation by collagen fibers, extensive inflammatory cell infiltration, and large-size tumor cells, such as Reed-Sternberg cells. These tissues stained strongly positive for PAX5 and CD30, weakly positive for CD15, and negative for Epstein-Barr viral RNA. We also found monoclonal gene rearrangement in the immunoglobulin heavy chain gene in the mediastinal large B-cell lymphoma, but no monoclonal gene rearrangement in the nodular sclerosis Hodgkin lymphoma. These findings suggested that these two lymphomas were not of a common clonal origin. The patient was treated by surgical excision of the mediastinal mass followed by radio-chemotherapy, and no metastasis or recurrence occurred during a follow-up period of 32 months. CONCLUSION: A review of previously reported cases indicated that the clinical manifestations and pathological features of discordant lymphoma are diverse due to variation in the types of lymphomas involved. Physicians must have an awareness of discordant lymphoma to avoid incorrect and missed diagnoses, especially considering that the true incidence may not be as low as previously believed.

Extragonadal malignant germ cell tumors: a clinicopathological and immunohistochemical analysis of 48 cases at a single Chinese institution.

Primary extragonadal malignant germ cell tumors (EMGCTs) are rare and characterized by the location in the midline of the body, including mediastinum, CNS, retroperitoneum and coccyx. EMGCTs present with different clinical and biologic characteristics in different tumor locations. Accurately diagnosing MEGCTs would be very difficult by performing on HE staining alone, and requires immunohistochemical verification. This study was to investigate the biological feature of EMGCTs and diagnostic value of immunohistochemical markers OCT3/4, CD117, PLAP, AFP, ß-HCG and CD30 in EMGCTs. A retrospective study was performed on 48 patients with EMGCTs. EMGCTs were found to occur predominantly in males, especially for mediastinal MGCTs. The tumor locations included mediastinum, CNS and retroperitoneum. The mediastinum and CNS were the most common sites of EMGCTs. Seminoma/germinomas (64.6%) was the most common histological subtypes of EMGCTs. Chest pain, dyspnea, cough and fever were the most common clinical presentations in mediastinal MGCTs. Headache, visual disturbances, endocrine abnormalities, and signs of increased intracranial pressure were common clinical symptoms in CNS MGCTs. Abdominal mass with or without pain, backache and weight loss were common clinical presentations in retroperitoneal MGCTs. PLAP, CD117 and OCT3/4 were highly expressed in seminomas/gernimomas. CD30, EMA and CK AE1/3 staining were positive in embryonal carcinoma. AFP and ß-HCG positive staining are characteristic in yolk sac tumors and choriocarcinoma, respectively. Patients with seminomas/germinomas had a better prognosis than those with NS/G-GCTs. Our finding suggests that the accurate diagnosis of EMGCTs is critical not only for predicting the tumor progression but also for patient management. Immunohistochemical markers have become an important tool in the diagnosis and differential diagnosis of EMGCTs.

Identification of Primary Mediastinal Large B-cell Lymphoma at Nonmediastinal Sites by Gene Expression Profiling.

Mediastinal involvement is considered essential for the diagnosis of primary mediastinal large B-cell lymphoma (PMBL). However, we have observed cases of diffuse large B-cell lymphoma (DLBCL) with features of PMBL but without detectable mediastinal involvement. The goal was to assess our previously established gene expression profiling (GEP) signature for PMBL in classifying these cases. In a large series of DLBCL cases, we identified 24 cases with a GEP signature of PMBL, including 9 cases with a submission diagnosis of DLBCL consistent with PMBL (G-PMBL-P) and 15 cases with a submission diagnosis of DLBCL. The pathology reviewers agreed with the diagnosis in the 9 G-PMBL-P cases. Among the other 15 DLBCL cases, 11 were considered to be PMBL or DLBCL consistent with PMBL, 3 were considered to be DLBCL, and 1 case was a gray-zone lymphoma with features intermediate between DLBCL and classical Hodgkin lymphoma. All 9 G-PMBL-P and 9 of the 15 DLBCL cases (G-PMBL-M) had demonstrated mediastinal involvement at presentation. Interestingly, 6 of the 15 DLBCL cases (G-PMBL-NM) had no clinical or radiologic evidence of mediastinal involvement. The 3 subgroups of PMBL had otherwise similar clinical characteristics, and there were no significant differences in overall survival. Genetic alterations of CIITA and PDL1/2 were detected in 26% and 40% of cases, respectively, including 1 G-PMBL-NM case with gain of PDL1/2. In conclusion, PMBL can present as a nonmediastinal tumor without evidence of mediastinal involvement, and GEP offers a more precise diagnosis of PMBL.

A large mediastinal benign myoepithelioma effacing the entire hemithorax: case report with literature review.

BACKGROUND: Myoepithelial neoplasms, although sometimes encountered in soft tissues are described very rarely in mediastinum and lung. We reported a rare case of such a tumor which was very large in size and not connected to respiratory tree. CASE PRESENTATION: A 24 year old male presented with blunt chest pain and respiratory distress. A CT scan was performed which showed large heterogeneously enhancing soft tissue mass occupying the left hemithorax. It measures 18.5 X 15.8 X 7.6. Thoracotomy with excision of the tumor was done. Operative findings include multilobulated and nodular large glistening white tumor located in anterior mediastinum adherent to parietal pleura and effacing the pulmonary parenchyma. However tumor was not connected or seems to originate from trachea or lung. Microscopic sections show neoplastic lesion composed of nests, cords and trabeculae of small to medium sized cells with round nuclei and clear cytoplasm. Background showed myxoid appearance with areas of cartilaginous differentiation. Immunohistochemical expression of CKAE1/AE3, p63, ASMA, S100 and GFAP favored the diagnosis of benign myoepithelioma. CONCLUSION: Myoepithelial tumors are rare soft tissue tumors thought to arise from stem cells capable of divergent differentiation and occur anywhere in the body. Histopathologic recognition of these tumors is essential as these tumors may behave in a benign fashion despite large sizes.